Novel Mechanisms in Ca2+ Homeostasis and Internal Store Refilling of Airway Smooth Muscle

Calcium is known to play a key role in excitation–contraction coupling of airway smooth muscle (ASM) and may also be important in other cellular responses, such as gene expression, migration, proliferation, and apoptosis. The sarcoplasmic reticulum acts as an agonist-releasable store of Ca2+ and as a sink to buffer changes in cytosolic [Ca2+]i. ASM also expresses, in great abundance, other Ca2+-mobilizing effectors such as voltage-dependent Ca2+ channels (Cav) and sodium/calcium exchangers (NCX) on the plasmalemma, as well as ryanodine receptors (RyRs) on the SR membrane. These three had long been held to be important in mediating electromechanical coupling (Cav), extrusion of cytosolic Ca2+ (NCX) and Ca2+-induced Ca2+ release (RyR), respectively. However, more recent data and careful consideration have challenged those associations. In this chapter, we explore the novel hypothesis that all three contribute to refilling of the SR, perhaps orchestrated or powered by electrical slow waves (which are also found in ASM of all species studied to date).